Among the greatest successes in the field of public health is widespread vaccination against a variety of formerly common infectious diseases. For example, public vaccination programs in the United States have eradicated smallpox and dramatically reduced the incidence of diseases such as measles, rubella, polio and diphtheria, among others. However, the development of novel vaccine compositions is still an active area of research. In particular, the development of effective vaccines for a number of diseases for which no clinically proven vaccine exists remains an important goal. For example, a vaccine which protects against infection by human immunodeficiency virus (HIV) is a primary goal in efforts to control the spread of AIDS. Also needed are vaccine compositions which have improved efficacy in comparison to vaccines in current use.
The efficacy of a vaccine for use in humans depends upon the ability of the vaccine formulation to elicit an immune response which is sufficient to provide protection against subsequent challenge with the pathogen. Experimental vaccines are typically evaluated first in vivo in small animals, such as mice, guinea pigs or rabbits. The assessment of the experimental vaccines generally relies upon measurements of serum antibody responses and, sometimes, antigen-specific lymphocyte proliferative responses. Vaccine formulations which are successful in these animal models are then tested in sub-human primates and, finally, in humans.
The assessment of a test vaccine in an animal model is costly and takes considerable time. Typically, several doses of vaccine are administered to the animal at intervals of several weeks. The immune response of primates to a given test vaccines is often less than that of smaller animals, and clinical studies in humans ultimately required to determine the efficacy of a test vaccine. In addition to the large cost associated with purchasing and housing animals for long periods of time, each step of the process requires a minimum of several months. Thus, the number of experimental vaccines which can be evaluated using prior art methods is necessarily limited, with the possible result that potentially useful vaccine formulations may never be tested.
There is, therefore, a need for an in vitro test for determining the human immune response to an experimental vaccine construct which would allow the rapid evaluation of large numbers of candidate vaccine compositions within a short time period and at reasonable cost.